STREAM trial final results show 9-month treatment for multi-drug resistant TB is as effective as 24-month treatment

Image copyright: The Union

 

Final results from Stage 1 of the STREAM trial show that a 9-11-month treatment regimen is as effective in treating multidrug-resistant tuberculosis (MDR-TB), when given under trial conditions, as the 20-24 month treatment regimen recommended in the 2011 World Health Organisation (WHO) guidelines. These results were published yesterday in the New England Journal of Medicine.

MDR-TB (TB that is resistant to at least the two first-line antibiotics isoniazid and rifampicin) affected almost half a million people in 2017 and has been declared a public health crisis by the WHO. The 20-24 month regimen used in many countries globally is costly, has significant side effects and the length of the regimen makes it hard for both patients and the health system. The regimen has an average treatment success rate of approximately 50 percent when used in real-world treatment settings.

Stage 1 of the STREAM trial tested whether a 9-11-month treatment regimen is as effective as the longer regimen under clinical trial conditions. Seven sites in Vietnam, Mongolia, South Africa, and Ethiopia participated in Stage 1.

424 participants were randomised to receive either:

  • Arm A: the standardised 20 to 24-month regimen in use at the study site (provided that it complied with WHO guidelines)
  • Arm B: a regimen consisting of clofazimine, ethambutol, pyrazinamide and high dose moxifloxacin,given for 9-11 months, supplemented by kanamycin, prothionamide, and high-dose isoniazid in the first four months.

The results showed that the 9-11month regimen was statistically non-inferior to the 20-24 month regimen. 78.8 percent of assessable participants in the 9-11 month regimen had a favourable outcome, compared to 79.8 percent in the longer regimen. The two regimens had similar levels of severe side-effects.

Electrocardiogram (ECG) monitoring was very useful very useful for detecting and preventing potential heart side-effects, and was required throughout treatment for patients on the 9-11 month regimen. Close monitoring would also be necessary if the regimen were to be used in routine programme settings.

I.D. Rusen, Project Director for the STREAM trial said: “Until now there has been a lack of strong supporting evidence to underpin MDR-TB treatment guidelines. The results from STREAM Stage 1 help to fill that gap.
Andrew Nunn, STREAM co-Chief Investigator from the MRC Clinical Trials Unit at UCL, said: “We know from programmatic data that the 20-24-month regimen has a number of major drawbacks, including the difficulty of completing such a long treatment, the significant side-effects of the drugs used and poor treatment outcomes. Shorter, more effective and safer regimens are urgently needed. The results from STREAM Stage 1 give TB programmes the option of a shorter regimen of comparable efficacy and safety to the long regimen.”

The STREAM Stage 1 trial was sponsored by The Union and Vital Strategies with key global partners, including the Medical Research Council Clinical Trials Unit at UCL, Liverpool School of Tropical Medicine and the Institute for Tropical Medicine.

Stage 1 of the Standardised Treatment Regimen of Anti-TB Drugs for Patients with MDR-TB (STREAM) trial was funded through the TREAT TB cooperative agreement with the U.S. Agency for International Development (USAID) with additional funding from the UK Medical Research Council and the UK Department for International Development (DFID).

Further information